In a practical situation, when radiation is received by radiation workers or members of the general public, the dose is delivered in a series of small dose-fractions or continuously at low dose-rate. By contrast, most carcinogenesis studies with experimental animals have involved single large doses of radiation. It is planned to use the recently developed powerful methods of in vitro oncogenic transformation to investigate the effect of dose fractionation and variations in dose-rate, both for x-rays and for cyclotron produced neutrons. The C3H 10T 1/2 cell line has been shown to be readily transformable with chemical carcinogens or ionizing radiations. The rate of transformations will be determined for single and split doses over a wide range of dose levels, both for x-rays and for neutrons. Preliminary experiments with x-rays indicate that at low dose levels below 100 rad, splitting the dose into two fractions separated by a time interval of 5 hours increases the incidence of transformed clones compared with the same total dose delivered in a single exposure. By contrast, at high doses, dose fractionation results in a decrease in the transformation rate. These findings, which have important implications in radiation protection and in the interpretation of risk estimates, will be confirmed and extended. In addition, the effect of continuous low dose-rate exposures will be investigated.